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Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells.

Holmdahl, Meirav LU ; Grubb, Anders LU and Holmdahl, Rikard LU (2004) In International Immunology 16(5). p.717-726
Abstract
Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on activation of CII-reactive T cells. Dendritic cells (DCs) are believed to play a crucial role in antigen-specific priming of T cells but it is still unclear how the CII-reactive T cells are primed since Langerhans cells (LCs) are poor antigen-presenting cells for CII. In the present study we show that LCs, treated with cysteine protease inhibitors, are able to process and present CII to T-cell hybridomas specific for the immune-dominant glycosylated 259–270 peptide bound to the MHC class II molecule Aq. Interestingly, the self (mouse) CII peptide could also now be efficiently presented. The poor presentation by LCs is a peptide-specific effect, since both bovine... (More)
Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on activation of CII-reactive T cells. Dendritic cells (DCs) are believed to play a crucial role in antigen-specific priming of T cells but it is still unclear how the CII-reactive T cells are primed since Langerhans cells (LCs) are poor antigen-presenting cells for CII. In the present study we show that LCs, treated with cysteine protease inhibitors, are able to process and present CII to T-cell hybridomas specific for the immune-dominant glycosylated 259–270 peptide bound to the MHC class II molecule Aq. Interestingly, the self (mouse) CII peptide could also now be efficiently presented. The poor presentation by LCs is a peptide-specific effect, since both bovine CII (bCII) (presenting a different peptide on H-2r) and ovalbumin could be efficiently presented, and blockage of cysteine proteases did not enhance antigen presentation. The enhanced CII-presentation by cysteine protease inhibition is seen mainly in LCs and not in antigen-primed B cells or macrophages. B cell and macrophage presentation of CII occur even without protease inhibition and are only to a minor extent influenced by cysteine protease inhibition. These data suggest that a LC deficiency in processing of the immune-dominant CII epitope in both CIA and RA may limit the exposure of this self-antigen to T cells, but that presentation can be overcome by modulation of the peptide proteolysis during CII processing. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Immunology
volume
16
issue
5
pages
717 - 726
publisher
Oxford University Press
external identifiers
  • wos:000221295100010
  • pmid:15096478
  • scopus:2442448511
ISSN
1460-2377
DOI
10.1093/intimm/dxh079
language
English
LU publication?
yes
id
56cf344a-b49a-4ecb-a77b-b6f232741370 (old id 122542)
date added to LUP
2007-07-05 10:27:32
date last changed
2017-01-01 04:42:57
@article{56cf344a-b49a-4ecb-a77b-b6f232741370,
  abstract     = {Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on activation of CII-reactive T cells. Dendritic cells (DCs) are believed to play a crucial role in antigen-specific priming of T cells but it is still unclear how the CII-reactive T cells are primed since Langerhans cells (LCs) are poor antigen-presenting cells for CII. In the present study we show that LCs, treated with cysteine protease inhibitors, are able to process and present CII to T-cell hybridomas specific for the immune-dominant glycosylated 259–270 peptide bound to the MHC class II molecule Aq. Interestingly, the self (mouse) CII peptide could also now be efficiently presented. The poor presentation by LCs is a peptide-specific effect, since both bovine CII (bCII) (presenting a different peptide on H-2r) and ovalbumin could be efficiently presented, and blockage of cysteine proteases did not enhance antigen presentation. The enhanced CII-presentation by cysteine protease inhibition is seen mainly in LCs and not in antigen-primed B cells or macrophages. B cell and macrophage presentation of CII occur even without protease inhibition and are only to a minor extent influenced by cysteine protease inhibition. These data suggest that a LC deficiency in processing of the immune-dominant CII epitope in both CIA and RA may limit the exposure of this self-antigen to T cells, but that presentation can be overcome by modulation of the peptide proteolysis during CII processing.},
  author       = {Holmdahl, Meirav and Grubb, Anders and Holmdahl, Rikard},
  issn         = {1460-2377},
  language     = {eng},
  number       = {5},
  pages        = {717--726},
  publisher    = {Oxford University Press},
  series       = {International Immunology},
  title        = {Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells.},
  url          = {http://dx.doi.org/10.1093/intimm/dxh079},
  volume       = {16},
  year         = {2004},
}